Department of Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, Japan.
J Gastroenterol. 2010 Oct;45(10):999-1007. doi: 10.1007/s00535-010-0245-1. Epub 2010 Apr 20.
Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 has been shown to elicit a Th2-like cytokine response in immune cells. In this study, we investigated IL-33 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-33 expression in human colonic subepithelial myofibroblasts (SEMFs).
IL-33 mRNA expression was determined by real-time polymerase chain reaction (PCR). IL-33 expression in the IBD mucosa was evaluated by immunohistochemical methods.
IL-33 mRNA expression was significantly elevated in active lesions from patients with ulcerative colitis (UC), but was not detected in inactive lesions from UC patients or in lesions from patients with either active or inactive Crohn's disease. Colonic SEMFs were identified as a major source of IL-33 in the mucosa. IL-1β and tumor necrosis factor-α (TNF-α) significantly enhanced IL-33 mRNA and protein expression in isolated colonic SEMFs. IL-1β and TNF-α did not affect IL-33 expression in intestinal epithelial cell lines (HT-29 and Caco-2 cells). This IL-1β- and TNF-α-induced IL-33 mRNA expression was mediated by p42/44 mitogen activated protein kinase (MAPK) pathway-dependent activation of nuclear factor (NF)-κB and activator protein (AP)-1.
IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.
白细胞介素（IL）-33 是一种细胞因子，属于 IL-1 家族。IL-33 已被证明可在免疫细胞中引发 Th2 样细胞因子反应。在这项研究中，我们研究了炎症性肠病（IBD）患者炎症黏膜中的 IL-33 表达，并表征了负责人结肠黏膜下肌成纤维细胞（SEMF）中 IL-33 表达的分子机制。
通过实时聚合酶链反应（PCR）测定 IL-33 mRNA 表达。通过免疫组织化学方法评估 IBD 黏膜中的 IL-33 表达。
溃疡性结肠炎（UC）患者的活动病变中 IL-33 mRNA 表达显著升高，但 UC 患者的非活动病变或克罗恩病患者的活动或非活动病变中未检测到。结肠 SEMF 被鉴定为黏膜中 IL-33 的主要来源。IL-1β 和肿瘤坏死因子-α（TNF-α）可显著增强分离的结肠 SEMF 中的 IL-33 mRNA 和蛋白表达。IL-1β 和 TNF-α 不会影响肠上皮细胞系（HT-29 和 Caco-2 细胞）中的 IL-33 表达。这种由 IL-1β 和 TNF-α 诱导的 IL-33 mRNA 表达是通过 p42/44 有丝分裂原激活蛋白激酶（MAPK）途径依赖性核因子（NF）-κB 和激活蛋白（AP）-1 的激活介导的。
源自结肠 SEMF 的 IL-33 可能在 UC 的病理生理学中起重要作用。
